Biased TCR repertoire in infiltrating lesional T cells in human bancroftian filariasis

To investigate the hypothesis that T cells recognizing specific Ags localiz e to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR V beta gene segments in lesions vs blood in individual patients by RT-PCR ELISA, V beta 14 and V beta 24 were overrepre sented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PNMC ratios for all V beta s for all, subje cts) in 50% and 40% of study subjects, respectively. Overrepresentation of these two V beta s did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criteri on for V beta 14 overrepresentation was shown to increase in tandem with ou r current concepts of disease progression (asymptomatic filariasis = 25%; c linical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with V beta 4 overrepr esentation, V beta 14 represented >20% of the entire lesional V beta repert oire. All but one of the 20 study subjects had at least one V beta gene seg ment that was overrepresented in tissue compared ffith PBMCs. Only a small number of V beta s, usually three or less, were overrepresented in any sing le filariasis patient, However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha; IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or wit h clinical filariasis, distinct and limited T cell populations are concentr ated in affected tissue.